Racila E, Scheuermann R H, Picker L J, Yefenof E, Tucker T, Chang W, Marches R, Street N E, Vitetta E S, Uhr J W
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
J Exp Med. 1995 Apr 1;181(4):1539-50. doi: 10.1084/jem.181.4.1539.
Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.
通过在肿瘤细胞攻击前用肿瘤免疫球蛋白（Ig）免疫BALB/c小鼠，可在小鼠B细胞淋巴瘤（BCL1）中诱导肿瘤休眠。在本报告中，我们研究了诱导休眠的免疫和细胞机制。将BCL1肿瘤细胞注射到用针对IgM或IgD上不同表位的抗体被动免疫的SCID小鼠中，这些抗体有无独特型（Id）免疫T淋巴细胞。结果表明，抗IgM抗体足以诱导休眠状态。针对包括IgD和CD44（Pgp1）在内的其他细胞表面分子的抗体对肿瘤生长没有影响。Id免疫T细胞自身对SCID小鼠的肿瘤生长也没有影响。然而，同时转移抗Id和Id免疫T细胞可增强休眠状态的诱导和持续时间。体外研究表明，抗IgM抗体在数小时内诱导凋亡，24小时内诱导细胞周期停滞。过度交联增加凋亡。FcγRII受体在负信号传导中作用很小或没有作用。在体外不产生负信号的抗体在体内不诱导休眠。结果表明，抗IgM通过作为IgM介导的信号转导途径的激动剂，在诱导BCL1肿瘤休眠中起决定性作用。
